Quantitation of irbesartan and major proteins in human plasma by mass spectrometry with time-of-flight analyzer

Abstract

A simple matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method was developed to analyze irbesartan in human plasma. Irbesartan is a kind of angiotensin II receptor blocker (ARB) and is used as an antihypertensive drug. MALDI-TOF MS is a rare application for clinical drug analysis in human plasma. After simple micro-liquid-liquid extraction, irbesartan-containing supernatant was spotted on a target plate, mixed with matrix and then detected by MALDI-TOF MS within the clinically therapeutic range. Furthermore, we used cheaper chemical analogues to label the major proteins in human plasma for protein quantitation. After enzyme digestion, peptide mixtures were injected into nanoliquid chromatography (nanoLC) coupled with tandem mass spectrometry (MS-MS). Protein identification could be carried out simultaneously by peptide sequencing and database searching. Chemical analogue labeling method is an alternative way for expensive isotope reagents. Quantity change of proteins before and after administration of irbesartan could be detected by this method. Application of these methods in human plasma demonstrated that these two micro-scale MS methods used for clinical drug monitoring, protein quantitation and identification are successful.